The role of cyclic nucleotide-generating systems to the functional operation of the central nervous system is being investigated from a number of standpoints: 1) The nature of the control of adenylate cyclase or phosphodiesterase activity by neurotransmitters, guanyl nucleotides, gangliosides, phospholipids, calcium ions, monovalent cations, proteases, and other factors. 2) The development of selective inhibitors for the two major phosphodiesterases in rat brain, namely a calcium-dependent and a calcium-independent enzyme. 3) The nature of the activation of adenylate cyclase by a selective alpha-adrenergic agonist, 6-fluoronorepinephrine. 4) The nature of the facilitation of beta-adrenergic, H2-histaminergic, and adenosine-mediated activation of cyclic AMP systems in brain slices and brain vesicular preparations by alpha-adrenergic, H1-histaminergic, and serotonergic agonists. 5) The adenosine-dependent desensitization of receptor-adenylate cyclase complexes in brain vesicular preparations. 6) The relationship of membrane potential to cyclic AMP levels in brain vesicular preparations. 7) The factors involved in glutamate or depolarizing agent-elicited accumulations of cyclic AMP in brain slices.